This Project will determine crystal structures of key proteins from a set of important eukaryotic pathogens. It will lay groundwork for subsequent biochemical studies and structure-based drug design targeting the corresponding diseases. These diseases include both major world scourges (malaria, sleeping sickness, Chagas' disease) and infections relevant to biodefense. The project is one component of collaboration involving multiple groups at the University of Washington, which jointly encompass the identification of relevant protein sequences from the target genomes, the expression and crystallization of protein expressed from these targets, and the identification of ligands that may be developed into lead compounds for drug design. The high-throughput technology developed within SGPP for structure determination will be combined with the output of large-scale chemical modeling and biochemical screening to generate three-dimensional structures for key proteins and protein:ligand complexes.